REFERENCES

1. Geng R, Li J, Yu C, et al. Knee osteoarthritis: current status and research progress in treatment (review). Exp Ther Med. 2023;26:481.

2. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. The Lancet. 2019;393:1745-59.

3. Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021;325:568.

4. Steinmetz JD, Culbreth GT, Haile LM, et al. Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5:e508-22.

5. Coppola C, Greco M, Munir A, et al. Osteoarthritis: insights into diagnosis, pathophysiology, therapeutic avenues, and the potential of natural extracts. Curr Issues Mol Biol. 2024;46:4063-105.

6. Ferreira De Meneses S, Rannou F, Hunter DJ. Osteoarthritis guidelines: barriers to implementation and solutions. Ann Phys Rehabil Med. 2016;59:170-3.

7. Van Den Bosch MHJ. Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease? Clin Exp Immunol. 2019;195:153-66.

8. Greene M, Loeser R. Aging-related inflammation in osteoarthritis. Osteoarthr Cartilage. 2015;23:1966-71.

9. Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthr Cartilage. 2020;28:555-61.

10. Kuppa SS, Kim HK, Kang JY, Lee SC, Seon JK. Role of mesenchymal stem cells and their paracrine mediators in macrophage polarization: an approach to reduce inflammation in osteoarthritis. Int J Mol Sci. 2022;23:13016.

11. Yang H, Xie Y, Yang D, Ren D. Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma. Oncotarget. 2017;8:25310-22.

12. Ma C, Wang X, He S, et al. Ubiquitinated AIF is a major mediator of hypoxia-induced mitochondrial dysfunction and pulmonary artery smooth muscle cell proliferation. Cell Biosci. 2022;12:9.

13. Liu Y, Zhang Z, Li T, Xu H, Zhang H. Senescence in osteoarthritis: from mechanism to potential treatment. Arthritis Res Ther. 2022;24:174.

14. Lepetsos P, Papavassiliou KA, Papavassiliou AG. Redox and NF-κB signaling in osteoarthritis. Free Radic Biol Med. 2019;132:90-100.

15. Feng W, Zhang Z, Zhao Z, et al. Biomaterial strategies in osteoarthritis: new insights bridging aging phenotypes and hypoxic microenvironment pathology. Adv Healthcare Mater. 2025;14:e01570.

16. Chen J, Deng M, Wang J, et al. Recent advances in injectable hydrogels for osteoarthritis treatments. Front Bioeng Biotechnol. 2025;13:1644222.

17. Perez-Terzic C, Childers MK. Regenerative rehabilitation: a new future? Am J Phys Med Rehab. 2014;93:S73-8.

18. Tan B, Zhang A, Yu L. Regenerative rehabilitation: mechanisms, clinical applications, and translational challenges. Regen Repair Rehabil. 2025;1:1-5.

19. Lu J, Deng S, Cheng H, Zhu J. Stem cell therapy for osteoarthritis: advances and challenges in clinical trials. Int J Surg. 2025;111:4815-7.

20. Gan X, Wang X, Huang Y, Li G, Kang H. Applications of hydrogels in osteoarthritis treatment. Biomedicines. 2024;12:923.

21. Chen J, Du C, Tang B, et al. Application and progress of smart hydrogel microspheres for regulating oxidative stress in osteoarthritis. Chem Eng J. 2025;507:160620.

22. Wang W, Jiang J, Yu H, Sun Y. Application and progress of smart hydrogels in regulating oxidative stress and improving the immune microenvironment in osteoarthritis. Chem Eng J. 2025;522:167273.

23. Lan X, Li L, Jia Q, et al. Physical modalities for the treatment of knee osteoarthritis: a network meta-analysis. Aging Clin Exp Res. 2025;37:121.

24. Jia Y, Le H, Wang X, et al. Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering. Front. Bioeng. Biotechnol. 2023;11:1271762.

25. Liu Y, Bai Y, Heng BC, et al. Biomimetic electroactive materials and devices for regenerative engineering. Nat Rev Electr Eng. 2025;2:188-204.

26. Choi SW, Guan W, Chung K. Basic principles of hydrogel-based tissue transformation technologies and their applications. Cell. 2021;184:4115-36.

27. Zhang Y, Lv J, Zhao J, Ling G, Zhang P. A versatile GelMA composite hydrogel: designing principles, delivery forms and biomedical applications. Eur Polym J. 2023;197:112370.

28. Li X, Wang F, Zhang X, et al. Ultrasound-responsive piezoelectric analgesic microspheres alleviate osteoarthritis pain. J Controlled Release. 2025;385:114049.

29. Highley CB, Prestwich GD, Burdick JA. Recent advances in hyaluronic acid hydrogels for biomedical applications. Curr Opin Biotechnol. 2016;40:35-40.

30. Wu D, Yang S, Gong Z, et al. Enhanced therapeutic potential of a self-healing hyaluronic acid hydrogel for early intervention in osteoarthritis. Mater Today Bio. 2024;29:101353.

31. Gu Z, Huang K, Luo Y, et al. Double network hydrogel for tissue engineering. WIREs Nanomed Nanobiotechnol. 2018;10:e1520.

32. Chen Q, Jin Y, Chen T, et al. Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis. Mater Today Bio. 2024;25:100993.

33. Xu Z, Liu J, Hu H, et al. Recent applications of stimulus-responsive smart hydrogels for osteoarthritis therapy. Front Bioeng Biotechnol. 2025;13:1539566.

34. Gou Y, Huang Y, Luo W, et al. Adipose-derived mesenchymal stem cells (MSCs) are a superior cell source for bone tissue engineering. Bioact Mater. 2024;34:51-63.

35. Bartold M, Gronthos S, Haynes D, Ivanovski S. Mesenchymal stem cells and biologic factors leading to bone formation. J Clin Periodontol. 2019;46 Suppl:12-32.

36. Almahasneh F, Abu-El-Rub E, Khasawneh RR. Mechanisms of analgesic effect of mesenchymal stem cells in osteoarthritis pain. World J Stem Cells. 2023;15:196-208.

37. Hamdalla HM, Ahmed RR, Galaly SR, et al. Assessment of the efficacy of bone marrow-derived mesenchymal stem cells against a monoiodoacetate-induced osteoarthritis model in wistar rats. Stem Cells Int. 2022;2022:1-14.

38. Kim J, Kim K, Yoon WK, Song S, Jin W. Intra-articular injection of mesenchymal stem cells after high tibial osteotomy in osteoarthritic knee: two-year follow-up of randomized control trial. Stem Cells Transl Med. 2022;11:572-85.

39. Wang Z, Hu Z, Niu L, Xu Y, Qi Y. Mesenchymal stem cell-derived exosomes for the treatment of knee osteoarthritis: a systematic review and meta-analysis based on rat model. Front Pharmacol. 2025;16:1588841.

40. Liu W, Jiang H, Chen J, et al. High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration. Mater Today Bio. 2025;30:101372.

41. Zhang X, Liu T, Ran C, et al. Immunoregulatory paracrine effect of mesenchymal stem cells and mechanism in the treatment of osteoarthritis. Front Cell Dev Biol. 2024;12:1411507.

42. Platas J, Guillén MI, Pérez Del Caz MD, et al. Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes. Aging. 2016;8:1703-17.

43. Huang Y, Wang Y, Yang G, et al. Modular hydrogel niche orchestrates microenvironment detoxification and stem cell redirecting toward precision osteoarthritis therapy. Bioact Mater. 2026;57:660-75.

44. Peng X, Song W, Yan Z, Zhai W, Ren L. Gelatin microcarriers as an effective adipose-derived stem cells delivery strategy in osteoarthritis treatment. Int J Biol Macromol. 2024;283:137524.

45. Selvadoss A, Baby HM, Zhang H, Bajpayee AG. Harnessing exosomes for advanced osteoarthritis therapy. Nanoscale. 2024;16:19174-91.

46. Wu C, He Y, Yao Y, Yang H, Lu F. Exosomes treating osteoarthritis: hope with challenge. Heliyon. 2023;9:e13152.

47. Duan L, Xu X, Xu L, et al. Exosome-mediated drug delivery for cell-free therapy of osteoarthritis. Curr Med Chem. 2021;28:6458-83.

48. Chen M, Wang Q, Wang Y, Fan Y, Zhang X. Biomaterials-assisted exosomes therapy in osteoarthritis. Biomed Mater. 2022;17:022001.

49. Zhang H, Wang G, Chen J, et al. Harnessing Bi-exosome combination alleviates osteoarthritis progression. Bioact Mater. 2026;58:701-18.

50. Deng S, Chen X, Cao H, et al. Self‐assembled bifunctional exosomes simplify chondrocyte-targeted sustained-release systems in decellularized cartilage microgels for synergistic osteoarthritis therapy. Small. 2025;21:e03492.

51. Felician MCP, Belotto R, Tardivo JP, Baptista MS, Martins WK. Photobiomodulation: cellular, molecular, and clinical aspects. J Photoch Photobio A. 2023;17:100197.

52. Liebert A, Capon W, Pang V, et al. Photophysical mechanisms of photobiomodulation therapy as precision medicine. Biomedicines. 2023;11:237.

53. De Freitas LF, Hamblin MR. Proposed mechanisms of photobiomodulation or low-level light therapy. IEEE J Sel Top Quantum Electron. 2016;22:348-64.

54. Lohr NL, Keszler A, Pratt P, Bienengraber M, Warltier DC, Hogg N. Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. J Mol Cell Cardiol. 2009;47:256-63.

55. Sharma SK, Kharkwal GB, Sajo M, et al. Dose response effects of 810 nm laser light on mouse primary cortical neurons. Lasers Surg Med. 2011;43:851-9.

56. Tim CR, Bossini PS, Kido HW, et al. Effects of low level laser therapy on inflammatory and angiogenic gene expression during the process of bone healing: a microarray analysis. J Photoch Photobio B. 2016;154:8-15.

57. Hong Y, Ji M, Su Y, Song C. Cartilage-targeted Au@Pt nanospheres with enhanced photothermal effect for promoting the recovery of osteoarthritis via ROS catalysis. Colloid Surface B. 2025;256:115036.

58. Chen F, Wang W, Zhao H, et al. MXene-based cartilage-adhesive microspheres for photothermal-controlled hydrophobic drug release and mesenchymal stem cell delivery in osteoarthritis. ACS Nano. 2025;19:20502-15.

59. Shi G, Jiang H, Yang F, et al. NIR-responsive molybdenum (Mo)-based nanoclusters enhance ROS scavenging for osteoarthritis therapy. Pharmacol Res. 2023;192:106768.

60. Zhou M, He Y, Zhang N, et al. Ultrasound-triggered diselenide bonds scission for on-demand drug release in osteoarthritis therapy. Adv Funct Mater. 2026;36:e27134.

61. Gong H, Zhang J, Fan Y, et al. Ultrasound-propelled antioxidant nanobowls for the treatment of osteoarthritis. Adv Funct Mater. 2025;36:e23507.

62. Ikenoue T, Trindade MCD, Lee MS, et al. Mechanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro. J Orthop Res. 2006;21:110-6.

63. Sun HB. Mechanical loading, cartilage degradation, and arthritis. Ann N Y Acad Sci. 2010;1211:37-50.

64. Gilbert SJ, Blain EJ. Cartilage mechanobiology: how chondrocytes respond to mechanical load. In: Mechanobiology in health and disease. Elsevier; 2018. pp. 99-126.

65. Mecchi L, Caron M, Welting T, Stoddart M. The impact of mechanical bioreactors on human mesenchymal stromal cells utilized for articular cartilage repair. Acta Biomater. 2026;210:40-56.

66. Zhou Y, Li M, Lin S, et al. Mechanical sensing protein PIEZO1 controls osteoarthritis via glycolysis mediated mesenchymal stem cells-Th17 cells crosstalk. Cell Death Dis. 2025;16:231.

67. Sun Q, Zhang Y, Hu B, et al. Development of a dual-responsive injectable GelMA/F127DA hydrogel for enhanced cartilage regeneration in osteoarthritis: harnessing MMP-triggered and mechanical stress-induced release of therapeutic agents. Int J Biol Macromol. 2025;304:140823.

68. Wang Y, Jin Z, Jia S, Shen P, Yang Y, Huang Y. Mechanical stress protects against chondrocyte pyroptosis through TGF-β1-mediated activation of Smad2/3 and inhibition of the NF-κB signaling pathway in an osteoarthritis model. Biomed Pharmacother. 2023;159:114216.

69. Alizadeh Sardroud H, Chen X, Eames BF. Applied compressive strain governs hyaline-like cartilage versus fibrocartilage-like ECM produced within hydrogel constructs. Int J Mol Sci. 2023;24:7410.

70. Wang T, Xie W, Ye W, He C. Effects of electromagnetic fields on osteoarthritis. Biomed Pharmacother. 2019;118:109282.

71. Cianni L, Di Gialleonardo E, Coppola D, et al. Current evidence using pulsed electromagnetic fields in osteoarthritis: a systematic review. JCM. 2024;13:1959.

72. Petecchia L, Sbrana F, Utzeri R, et al. Electro-magnetic field promotes osteogenic differentiation of BM-hMSCs through a selective action on Ca2+-related mechanisms. Sci Rep. 2015;5:13856.

73. Varani K, Vincenzi F, Ravani A, et al. Adenosine receptors as a biological pathway for the anti-inflammatory and beneficial effects of low frequency low energy pulsed electromagnetic fields. Mediators Inflamm. 2017;2017:1-11.

74. Wang A, Ma X, Bian J, et al. Signalling pathways underlying pulsed electromagnetic fields in bone repair. Front Bioeng Biotechnol. 2024;12:1333566.

75. Li Y, Li L, Li Y, et al. Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field. Bioact Mater. 2023;22:312-24.

76. Deng C, Li Z, Lu L, et al. Sophisticated magneto-mechanical actuation promotes in situ stem cell assembly and chondrogenesis for treating osteoarthritis. ACS Nano. 2023;17:21690-707.

77. Zhou J, Ning E, Lu L, Zhang H, Yang X, Hao Y. Effectiveness of low-intensity pulsed ultrasound on osteoarthritis: molecular mechanism and tissue engineering. Front Med. 2024;11:1292473.

78. Jia W, Zhou Z, Zhan W. Musculoskeletal biomaterials: stimulated and synergized with low intensity pulsed ultrasound. JFB. 2023;14:504.

79. Yang S, Kuo C, Chang SJ, et al. Does Low-intensity pulsed ultrasound treatment repair articular cartilage injury? A rabbit model study. BMC Musculoskelet Disord. 2014;15:36.

80. Wei Y, Li Z, Yu T, et al. Ultrasound-activated piezoelectric biomaterials for cartilage regeneration. Ultrason Sonochem. 2025;117:107353.

81. Kooiman K, Roovers S, Langeveld SA, et al. Ultrasound-responsive cavitation nuclei for therapy and drug delivery. Ultrasound Med Biol. 2020;46:1296-325.

82. Marcotulli M, Barbetta A, Scarpa E, et al. Jingle cell rock: steering cellular activity with low-intensity pulsed ultrasound (LIPUS) to engineer functional tissues in regenerative medicine. Ultrasound Med Biol. 2024;50:1973-86.

83. Pan C, Lu F, Hao X, et al. Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP-RIPK1-NF-κB axis and influencing autophagy. J Transl Med. 2024;22:286.

84. Zheng T, Huang Y, Zhang X, Cai Q, Deng X, Yang X. Mimicking the electrophysiological microenvironment of bone tissue using electroactive materials to promote its regeneration. J Mater Chem B. 2020;8:10221-56.

85. Wang X, Stefanello ST, Shahin V, Qian Y. From mechanoelectric conversion to tissue regeneration: translational progress in piezoelectric materials. Adv Mater. 2025;37:2417564.

86. Tandon B, Blaker JJ, Cartmell SH. Piezoelectric materials as stimulatory biomedical materials and scaffolds for bone repair. Acta Biomater. 2018;73:1-20.

87. Yu D, Li L, Cui X, et al. Synergistic piezoelectricity and lubrication in an injectable hydrogel for osteochondral regeneration. Adv Funct Mater. 2026;36:e75561.

88. Jacob J, More N, Kalia K, Kapusetti G. Piezoelectric smart biomaterials for bone and cartilage tissue engineering. Inflamm Regener. 2018;38:2.

89. Vinikoor T, Dzidotor GK, Le TT, et al. Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment. Nat Commun. 2023;14:6257.

90. Szponder T, Latalski M, Danielewicz A, et al. Osteoarthritis: pathogenesis, animal models, and new regenerative therapies. JCM. 2022;12:5.

91. Aswathy SH, Narendrakumar U, Manjubala I. An overview of approaches and evaluation methods for tissue-engineered articular cartilage constructs in animal models. Ann Biomed Eng. 2025;53:3009-30.

92. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthrit Care Res. 2020;72:149-62.

93. Nelligan RK. Appraisal of Clinical Practice Guideline: National Institute for Health and Care Excellence (NICE) Clinical Practice Guideline for osteoarthritis in over 16s: diagnosis and management. J Physiother. 2023;69:196.

94. Abafita BJ, Singh A, Aitken D, et al. Yoga or strengthening exercise for knee osteoarthritis: a randomized clinical trial. JAMA Netw Open. 2025;8:e253698.

95. Cao M, Ou Z, Sheng R, et al. Efficacy and safety of mesenchymal stem cells in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Stem Cell Res Ther. 2025;16:122.

96. Gupta PK, Maheshwari S, Cherian JJ, et al. Two years efficacy and safety outcomes of using allogeneic, pooled mesenchymal stromal cells for osteoarthritis of knee in a double-blind randomized placebo-controlled phase 3 study. Osteoarthr Cartil Open. 2026;8:100723.

97. Yamagami R, Terao T, Kasai T, et al. Baseline magnetic resonance imaging findings associated with short-term clinical outcomes after intraarticular administration of autologous adipose-derived stem cells for knee osteoarthritis. Regen Ther. 2025;28:227-34.

98. Iordan DA, Coman M, Hrisca-Eva O, Stavrică-George A, Gherghin A, Onu I. Enhanced synovial fluid rheology in moderate knee osteoarthritis through combined intra-articular hyaluronic acid and multimodal physiotherapy: a monocentric observational study. JCM. 2025;14:6051.

99. ClinicalTrials. gov. NCT06773676: Evaluating the effectiveness of using a home laser device to treat patients with knee osteoarthritis.

100. ClinicalTrials. gov. NCT07443462: Evaluation of the effects of pulsed electromagnetic field on inflammatory knee osteoarthritis.

101. ClinicalTrials. gov. NCT06937528: Use of extracellular vesicles (EV) for knee osteoarthrosis.

102. ClinicalTrials. gov. NCT05933434: Allogenic mesenchymal stem cell intraarticular injection for knee osteoarthritis therapy (STEMJOINT).

103. ClinicalTrials. gov. NCT06463847: Phase I clinical trial of UC-MSCs in the treatment of knee osteoarthritis.

104. ClinicalTrials. gov. NCT07547735: Phase II CLINICAL Trial of UC-MSCs in the treatment of knee osteoarthritis.

105. ClinicalTrials. gov. NCT07542808: An open-label, double-treatment group study to evaluate the efficacy and safety of human allogeneic bone-marrow-derived mesenchymal stromal cell product Stromaforte compared with hyaluronic acid for the treatment of knee osteoarthritis.

106. Calvet J, García-Manrique M, Berenguer-Llergo A, et al. Metabolic and inflammatory profiles define phenotypes with clinical relevance in female knee osteoarthritis patients with joint effusion. Rheumatology. 2023;62:3875-85.

107. Zhu Z, Yu Q, Leng X, et al. Low-dose methotrexate for the treatment of inflammatory knee osteoarthritis: a randomized clinical trial. JAMA Intern Med. 2025;185:808.

108. Li H, Xiang D, Gong C, Wang X, Liu L. Naturally derived injectable hydrogels with ROS-scavenging property to protect transplanted stem cell bioactivity for osteoarthritic cartilage repair. Front Bioeng Biotechnol. 2023;10:1109074.

109. Li B, Wang F, Hu F, et al. Injectable “nano-micron” combined gene-hydrogel microspheres for local treatment of osteoarthritis. NPG Asia Mater. 2022;14:1.

110. Feng J, Deng X, Hao P, et al. Intra-articular injection of platinum nanozyme-loaded silk fibroin/pullulan hydrogels relieves osteoarthritis through ROS scavenging and ferroptosis suppression. Int J Biol Macromol. 2024;280:135863.

111. Wang H, Ma B, Wang G, et al. Dose-response relationships of resistance training in adults with knee osteoarthritis: a systematic review and meta-analysis. J Geriatr Phys Ther. 2023.

112. De Wit J, Haber T, Hall M, et al. Association between prescribed dosage of resistance exercise and change in pain and physical function in knee osteoarthritis: a systematic review with meta-regression. Musculoskeletal Care. 2025;23:e70110.

113. Jorge AES, Dantas LO, Aburquerque-Sendín F, et al. Photobiomodulation does not provide incremental benefits to patients with knee osteoarthritis who receive a strengthening exercises program: a randomized controlled trial. Braz J Phys Ther. 2023;27:100519.

114. Nanus DE, Badoume A, Wijesinghe SN, et al. Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets. eBioMedicine. 2021;72:103618.

115. Wijesinghe SN, Badoume A, Nanus DE, et al. Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets. Clin Transl Med. 2023;13:e1232.

116. Wang M, Tan G, Jiang H, et al. Molecular crosstalk between articular cartilage, meniscus, synovium, and subchondral bone in osteoarthritis. Bone Joint Res. 2022;11:862-72.

117. Rebelatto CLK, Boldrini-Leite LM, Daga DR, et al. Quality control optimization for minimizing security risks associated with mesenchymal stromal cell-based product development. Int J Mol Sci. 2023;24:12955.

118. Williams S, Fernandez-Rhodes M, Law A, Peacock B, Lewis MP, Davies OG. Comparison of extracellular vesicle isolation processes for therapeutic applications. J Tissue Eng. 2023;14:20417314231174609.

119. Figueroa-Valdés AI, Luz-Crawford P, Herrera-Luna Y, et al. Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis. J Nanobiotechnol. 2025;23:13.

120. Binvignat M, Pedoia V, Butte AJ, et al. Use of machine learning in osteoarthritis research: a systematic literature review. RMD Open. 2022;8:e001998.

121. Lee DW, Han HS, Ro DH, Lee YS. Development of the machine learning model that is highly validated and easily applicable to predict radiographic knee osteoarthritis progression. J Orthop Res. 2024;43:128-38.

Science Orthopedics
ISSN : XXXX-XXXX (Coming soon)
Navigation
Navigation